1J1C,3EB0,3E3P,1PYX,1GNG,1O9U


Conserved Protein Domain Family
STKc_GSK3

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cd14137: STKc_GSK3 
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The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3
STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 271039
View PSSM: cd14137
Aligned: 86 rows
Threshold Bit Score: 334.856
Threshold Setting Gi: 17510851
Created: 5-Jul-2006
Updated: 2-Mar-2014
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 18 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:1J1C_B; Human GSK3beta monomer binds MgADP; defined at 4A contacts.
    View structure with Cn3D
  • Structure:1PYX; Human GSK3beta dimer binds to AMP-PNP molecules; defined at 4A contacts.
    View structure with Cn3D
  • Structure:3EB0_A; Cryptosporidium parvum GSK3 binds Indirubin E804 inhibitor; defined at 4A contacts.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                     ####    #               # #                           #            
1J1C_B        51 PQEVSYTDTK--VIGNGSFGVVYQAKLCds---gELVAIKKVLQDkrFKNRELQIMRKLD---HCNIVRLRYFFYSSgek 122 human
CAB01863      32 EVEIQFTNLQ--LIGTGSFGAVYKAVLRen---dEPIAIKKIKVDdrFKSRELTIMHEMD---HPNIIRLLYYYVMQq-- 101 nematode
CAA20977      22 RVGMQMANLR--LHARGVFSNVYRGTILspg-teQEIAIKKTWPKtpYRNFELLFLSGLRrkpHKNIVQMLFAFSRNtts 98  nematode
NP_492689     19 GKDMHLNLHHmnLFATGAFSNVYRGVAQtesnqeIDIVIKKTWPRhkGCPMEVKILGQLGklkHRNIVRLLYSYQKQhe- 97  nematode
T22168        16 NKKVMLKIEEvhLHSCGVFSNVYKGILRep--heKNIAIKKSWPEkgERNFEFIFLTGRErtkHKNVIHMIFAFSHSyg- 92  nematode
XP_001321319  15 QPLEGYTLVK--TVGVGTFGAVFLCNNAk----gEPVAIKKVFMDpkFKSRELQLVSRLQ---HPNNLVYIGHKFINegq 85  Trichomonas vag...
XP_001309059  32 SKKRKYLGYR--LIGSGTFGSVYKARTIa----gKVVAIKSVKQDpqYKNRELEILKILH---SRYCIKLKDHYFTRknn 102 Trichomonas vag...
XP_001322268  33 NSKFKYRVVQ--HIGSGAFGTVFQSISPt----gNIVAVKKVFQNphFKNRELEVLKALK---SPNCLSLHDYYTEKesg 103 Trichomonas vag...
XP_001326226  12 DENLGYQTLC--VSGIGTFGAVFKVQDDk----gEVYAIKKVWLNprFKNRESQITPLLA---HPNCLHCYKSFITNegp 82  Trichomonas vag...
XP_001306515  21 ENTDKYRVIE--KIGSGTFGNIYAIEYYd----rRRLALKKVLQDpkYKNRELTMIQALR---HPNCLKLHQYELKReg- 90  Trichomonas vag...
Feature 1                       ####  #                                            # ## #        
1J1C_B       123 ------kdEVYLNLVLDYVPETVYRVARHYsrakqtLPVIYVKLYMYQLFRSLAYIHSFGICHRDIKPQNLLLDPdtAVL 196 human
CAB01863     102 --------ENCLNFVMEFMPKDLAYVHRQFahndkqMPAYSIKLYMFQLLRGIGFLHLHNIVHRDIKPKNLLVDEsnGIL 173 nematode
CAA20977      99 geglemkhSFCESYVFGFMPYTLQNILKKTr-----LAEVDMKLYTWQLFEGIRYLQAHMIVHRDIKPVNILVDVdkGTL 173 nematode
NP_492689     98 -------gRICLALIFEYIPLNLYQFLKDKnr---rIDIVEVKLIVWQLFRGQAHLEKADICHRDIKPQNLLYNAetGLL 167 nematode
T22168        93 -------tKVCESYVFDYMPNTLAEVIRQK------LTDLDIRLYTWQIFSGLKYLEEHRVVHRDLKPVNILVDHdtGFL 159 nematode
XP_001321319  86 ------rqHKFLILITDYLPDSLPMFMSKFp----fPPPLYVKLWGYQMFSGLAYLHAHSIAHRDIKPSNVLVDPddGRL 155 Trichomonas vag...
XP_001309059 103 ------gkDVYLNIVMDYFPYTVHSYTMKLrdqqkrIGNTLLKILAYQIFAGLRYLHAKGIVHRDIKPENIMFSPvtGKL 176 Trichomonas vag...
XP_001322268 104 ------tdNTYLFLVIEFLPMSLRHCIKESrlfsnkFDPILHKLYSYQILTGLRDIHALGIAHRDIKPENILVNPlhGEI 177 Trichomonas vag...
XP_001326226  83 ------nrDAYFHLVTDFLPEDLEKLASVKs----pIDMRFVKIFGYQLFAGLCYLHHFGLCHRDIKPSNVLIDQndGRC 152 Trichomonas vag...
XP_001306515  91 -------dQEFLYIFTDLLPTDLHKYLRKNk-----ITTSLAKIFGYQLFNGLDYLHKINITHRDIKSSNILVDPdtGIL 158 Trichomonas vag...
Feature 1           #                                                                            
1J1C_B       197 KLCDFGSAKQLVRgEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLg-QPIFPGDSGVDQLVEIIKVLGT 275 human
CAB01863     174 KICDFGSAKRLEKnEPNITYICSRYYRAPELIFGSKNYDTSIDTWSVGTVVGELLHn-SPIFLADSAVDILALQIKAFGT 252 nematode
CAA20977     174 KIADFGSAKVVLRgSSSTSYQVTRFYRPPELLLDAKEYYWMVDVWSAGCCVGEMMKg-KVLFPGASIKIMLKLIVQAIGL 252 nematode
NP_492689    168 KISDFGSSSIQSTkSPQQSYHVTRYYRPPELILGSKYYGCKIDTWSCGCVFGELLKg-GIILAGKSSNNQAEVIFDMLGY 246 nematode
T22168       160 KISDFGSVKIIVKgKANNHYQVTRFYRPPELLQKAMEYNCTVDVWSAGCIMAEMVKr-RVVFPGRDSAQQMKLYCRCFGV 238 nematode
XP_001321319 156 QLCDFGSAKFLLPgEKSVSYIATRNYRAPELLLDCPAYTFSIDVWSAGCVLAELFLqgRSLFNGRNNSELLTSIVKTIGS 235 Trichomonas vag...
XP_001309059 177 KITDFGSAKVIKPgDTSVSYIASRFYRAPELILGCEQYTGAIDVWAAGCVIAEMLRmgEVLFEGMTGTGQIIPIIQLLGK 256 Trichomonas vag...
XP_001322268 178 KICDFGSAKFILNdRNSVPEVGSLNYRAPELLLGNRTYSTEIDIWAAGCVIAEMVLdnISMFPGTNDTNQMEGIVKVLGQ 257 Trichomonas vag...
XP_001326226 153 QLCDFGSAKFLVEnVKNVSYIATRSYRAPELILDCKTYNTKIDVWSAGCVLAELVLh-TILFNGTKGEEVLERITGIIGM 231 Trichomonas vag...
XP_001306515 159 KICDFGSAKELKInEASVSYISTRSYRAPELLYESQFYTSKIDVWAAGCVLSEMFKggDEIFHADSNQSLKQIILNFIGT 238 Trichomonas vag...
Feature 1                                                                                        
1J1C_B       276 PTReQIREMNPny--------------------teFKFPQ--IKAHPW-TKVFRpr----tPPEAIALCSRLLEYTPTAR 328 human
CAB01863     253 PSKeDMAKWNYey--------------------vhIPYDT--ITGVGI-QKFIGrk----lSLSTLELLNSLMKMDPKLR 305 nematode
CAA20977     253 PSArDLDYMKVss--------------------miDQQSA--VKVIGL-KEVLGt-----eNQEWADFLGAILRYRPRER 304 nematode
NP_492689    247 PTDsDVSSMKVsstklqevldsyeynkskttadltYLYTQtvIYQKDRrTTVYNtkieqddMKESVAVLLQILVYNPNKR 326 nematode
T22168       239 PTEqDILAMKGerle-----------------nelWKFTK--GFGLQR-LVTEI-------TPDQLQFIKRILVYTPEKR 291 nematode
XP_001321319 236 PNPeDLESFESsk---------------------rFTQFG--IKGMTL-KAALPsf----tPPEFIDLLEKIFIFNVKKR 287 Trichomonas vag...
XP_001309059 257 PTQsDLSSFQHtapv-----------------ptsLTKPI--IKLEDQ-LPKTT-------NSKLIALLKQIFVYNPTKR 309 Trichomonas vag...
XP_001322268 258 PTPeEDKSFPHp-----------------------IPFPNe-EKIADI-SIILPyk----cDPLLIDLLKSIFVYNPSKR 308 Trichomonas vag...
XP_001326226 232 PKIgDLDTFQHn----------------------lPLIFI--GPRYTKlQNEFPpd----tDPEFLDLLNHIFVWNVNNR 283 Trichomonas vag...
XP_001306515 239 PTIsDFHDMNL------------------------QLQPQfyHPGIGI-EHAFNep----lDPLLLDLLKKIFVYSPVLR 289 Trichomonas vag...
Feature 1                       
1J1C_B       329 LTpLEACAHSFFDEL 343 human
CAB01863     306 IKpYEALTLPYFDDL 320 nematode
CAA20977     305 LHgPKLLSHPFFDLI 319 nematode
NP_492689    327 LSgIEILTHPYFNVL 341 nematode
T22168       292 LHgKQLLQDDFFQTK 306 nematode
XP_001321319 288 YTaVDCMRHPFFADL 302 Trichomonas vaginalis G3
XP_001309059 310 ITaAQCLQHPYFEDL 324 Trichomonas vaginalis G3
XP_001322268 309 PTaAQLMKHPYFKSL 323 Trichomonas vaginalis G3
XP_001326226 284 YSaADCMRHPFFKDV 298 Trichomonas vaginalis G3
XP_001306515 290 YTaEQAKYHPFFAEV 304 Trichomonas vaginalis G3

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